Perinatal hypoxic-ischemic encephalopathy and neuroprotective peptide therapies: A case for cationic arginine-rich peptides (CARPs)

Adam B. Edwards, Ryan S. Anderton, Neville W. Knuckey, Bruno P. Meloni

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is only used for term infants (>36 weeks gestation) in tertiary hospitals and improves outcomes in only 30% of patients. For these reasons, a more effective and easily administrable pharmacological therapeutic agent, that can be used in combination with hypothermia or alone when hypothermia cannot be applied, is urgently needed to treat pre-term (≤36 weeks gestation) and term infants suffering HIE. Several recent studies have demonstrated that cationic arginine-rich peptides (CARPs), which include many cell-penetrating peptides [CPPs; e.g., transactivator of transcription (TAT) and poly-arginine-9 (R9; 9-mer of arginine)], possess intrinsic neuroprotective properties. For example, we have demonstrated that poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer (R18D) are neuroprotective in vitro following neuronal excitotoxicity, and in vivo following perinatal hypoxia-ischemia (HI). In this paper, we review studies that have used CARPs and other peptides, including putative neuroprotective peptides fused to TAT, in animal models of perinatal HIE. We critically evaluate the evidence that supports our hypothesis that CARP neuroprotection is mediated by peptide arginine content and positive charge and that CARPs represent a novel potential therapeutic for HIE.

Original languageEnglish
Article number147
JournalBrain Sciences
Volume8
Issue number8
DOIs
Publication statusPublished - 7 Aug 2018

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Brain Hypoxia-Ischemia
Arginine
Peptides
Hypothermia
Trans-Activators
Therapeutics
Cell-Penetrating Peptides
Pregnancy
Cerebral Palsy
Tertiary Care Centers
Intellectual Disability
Survivors
Epilepsy
Ischemia
Animal Models
Newborn Infant
Pharmacology
Morbidity

Cite this

@article{889845c4a53d40fea8a3e98f19555bd5,
title = "Perinatal hypoxic-ischemic encephalopathy and neuroprotective peptide therapies: A case for cationic arginine-rich peptides (CARPs)",
abstract = "Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is only used for term infants (>36 weeks gestation) in tertiary hospitals and improves outcomes in only 30{\%} of patients. For these reasons, a more effective and easily administrable pharmacological therapeutic agent, that can be used in combination with hypothermia or alone when hypothermia cannot be applied, is urgently needed to treat pre-term (≤36 weeks gestation) and term infants suffering HIE. Several recent studies have demonstrated that cationic arginine-rich peptides (CARPs), which include many cell-penetrating peptides [CPPs; e.g., transactivator of transcription (TAT) and poly-arginine-9 (R9; 9-mer of arginine)], possess intrinsic neuroprotective properties. For example, we have demonstrated that poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer (R18D) are neuroprotective in vitro following neuronal excitotoxicity, and in vivo following perinatal hypoxia-ischemia (HI). In this paper, we review studies that have used CARPs and other peptides, including putative neuroprotective peptides fused to TAT, in animal models of perinatal HIE. We critically evaluate the evidence that supports our hypothesis that CARP neuroprotection is mediated by peptide arginine content and positive charge and that CARPs represent a novel potential therapeutic for HIE.",
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language = "English",
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journal = "Brain Sciences",
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Perinatal hypoxic-ischemic encephalopathy and neuroprotective peptide therapies : A case for cationic arginine-rich peptides (CARPs). / Edwards, Adam B.; Anderton, Ryan S.; Knuckey, Neville W.; Meloni, Bruno P.

In: Brain Sciences, Vol. 8, No. 8, 147, 07.08.2018.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Perinatal hypoxic-ischemic encephalopathy and neuroprotective peptide therapies

T2 - A case for cationic arginine-rich peptides (CARPs)

AU - Edwards, Adam B.

AU - Anderton, Ryan S.

AU - Knuckey, Neville W.

AU - Meloni, Bruno P.

PY - 2018/8/7

Y1 - 2018/8/7

N2 - Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is only used for term infants (>36 weeks gestation) in tertiary hospitals and improves outcomes in only 30% of patients. For these reasons, a more effective and easily administrable pharmacological therapeutic agent, that can be used in combination with hypothermia or alone when hypothermia cannot be applied, is urgently needed to treat pre-term (≤36 weeks gestation) and term infants suffering HIE. Several recent studies have demonstrated that cationic arginine-rich peptides (CARPs), which include many cell-penetrating peptides [CPPs; e.g., transactivator of transcription (TAT) and poly-arginine-9 (R9; 9-mer of arginine)], possess intrinsic neuroprotective properties. For example, we have demonstrated that poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer (R18D) are neuroprotective in vitro following neuronal excitotoxicity, and in vivo following perinatal hypoxia-ischemia (HI). In this paper, we review studies that have used CARPs and other peptides, including putative neuroprotective peptides fused to TAT, in animal models of perinatal HIE. We critically evaluate the evidence that supports our hypothesis that CARP neuroprotection is mediated by peptide arginine content and positive charge and that CARPs represent a novel potential therapeutic for HIE.

AB - Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is only used for term infants (>36 weeks gestation) in tertiary hospitals and improves outcomes in only 30% of patients. For these reasons, a more effective and easily administrable pharmacological therapeutic agent, that can be used in combination with hypothermia or alone when hypothermia cannot be applied, is urgently needed to treat pre-term (≤36 weeks gestation) and term infants suffering HIE. Several recent studies have demonstrated that cationic arginine-rich peptides (CARPs), which include many cell-penetrating peptides [CPPs; e.g., transactivator of transcription (TAT) and poly-arginine-9 (R9; 9-mer of arginine)], possess intrinsic neuroprotective properties. For example, we have demonstrated that poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer (R18D) are neuroprotective in vitro following neuronal excitotoxicity, and in vivo following perinatal hypoxia-ischemia (HI). In this paper, we review studies that have used CARPs and other peptides, including putative neuroprotective peptides fused to TAT, in animal models of perinatal HIE. We critically evaluate the evidence that supports our hypothesis that CARP neuroprotection is mediated by peptide arginine content and positive charge and that CARPs represent a novel potential therapeutic for HIE.

KW - Animal models

KW - Birth asphyxia

KW - Cationic arginine-rich peptides

KW - Hypoxia-ischemia

KW - Hypoxic-ischemic encephalopathy

KW - Neuroprotection

UR - http://www.scopus.com/inward/record.url?scp=85051490694&partnerID=8YFLogxK

U2 - 10.3390/brainsci8080147

DO - 10.3390/brainsci8080147

M3 - Review article

VL - 8

JO - Brain Sciences

JF - Brain Sciences

SN - 2076-3425

IS - 8

M1 - 147

ER -